High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement

Abstract

High-dose melphalan (HDM) plus stem cell transplantation is an effective treatment for light-chain amyloidosis (AL), but is associated with high treatment-related mortality in patients with cardiac involvement. We studied 187 patients with cardiac involvement with AL who underwent HDM between 1996 and 2008. The median age was 57 years and the median time from diagnosis to HDM was 3.6 months. Half of the patients received reduced-dose melphalan (100-160 mg/m(2)). The median overall survival (OS) was 66 months, 54 months from diagnosis and HDM, respectively, and 91 patients (49%) were alive at the last follow-up 52 months (median) from HDM. Thirty patients (16%) died within 100 days of transplantation; only low serum albumin predicted early deaths. Overall, hematologic response (HR) and cardiac responses were seen in 66% and 41% of patients, respectively. The median OS for patients with and without HR was not reached and 22 months, respectively (P < .01); and for those with any decrease and no decrease in N-terminal-pro-brain natriuretic peptide was not reached and 26 months, respectively (P < .01). In multivariate analysis of baseline factors, only reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival.

Figure 1

Patient disposition and impact of hematological response on overall survival following stem cell transplantation. (A) Number of patients surviving at least 100 days after transplantation and those evaluable for hematologic and cardiac responses. (B) Kaplan-Meier curves comparing OS between patients with HR and those with no HR. The median OS for patients with (n = 124) and without (n = 33) an HR was 98 months (95% CI, 70 [NR]) and 28 months (95% CI, 14-42), respectively (P < .001). (C) Kaplan-Meier curves comparing TTNT between patients with HR and those with no HR. The median TTNT was 62 months for the responders compared with 24 months (95% CI, 15 [NR]) for those with no hematologic PR (P < .001). (D) Kaplan-Meier curves comparing OS between patients with CR and those with no CR. The median OS for patients with (n = 56) and without (n = 101) a CR was NR (95% CI, 98 [NR]) and 45 months (95% CI, 33-69), respectively (P < .001).

Figure 2

Impact of organ response on overall survival following stem cell transplantation. (A) Kaplan-Meier curves comparing OS between patients with cardiac response and those with no cardiac response. Among the 148 patients evaluable for a cardiac response, the median OS for patients with (n = 60) and without (n = 88) a cardiac response was NR and 58 months (95% CI, 38-75), respectively (P < .001). (B) Kaplan-Meier curves comparing OS between patients with a decrease in NT-ProBNP and those with no decrease. Among the 84 patients with available NT-ProBNP values at baseline and after HDM, the median OS for patients with (n = 58) and without (n = 26) any decrease in NT-ProBNP was NR and 42 months, respectively (P < .001). (C) Kaplan-Meier curves comparing the OS between patients with a ≥ 30% decrease in NT-ProBNP and those with a < 30% decrease. The median OS from HDM was NR for the group with a ≥ 30% decrease compared with 42 months for the remaining patients.